Abstract

The 5′‐untranslated region (UTR) consists of the leading part of a cellular messenger ribonucleic acid (mRNA) from the 5′
end to the translation start codon AUG. Precursor mRNA is posttranscriptionally modified by the removal of introns and by
the addition at the 5′ end of a 7‐methyl‐guanylate cap structure, which has a crucial role in translation initiation and regulating
transcript stability. 5′‐UTRs and 3′‐UTRs are deeply involved in posttranscriptional regulation of gene expression through
specific motifs or RNA base modifications that can affect mRNA stability, subcellular localisation, nuclear export, tissue
specificity and efficiency of translation.

5‐UTR regulation of translation is modulated by several cis‐acting elements that may also interact with trans acting factors
such as proteins or microRNAs. The best studied elements are secondary structures that affect ribosome scanning efficiency
(i.e. iron‐responsive element), internal ribosome entry sites (IRESs) and upstream open reading frames (uORFs).

Key Concepts

5′‐UTRs are involved in posttranscriptional regulation of gene expression.

Elements located in 5′‐UTRs interfere with ribosome scanning and modulate translation of main AUG.

Secondary structures can interfere with ribosome scanning and can be stabilised or destabilised by protein or RNA interaction.

Figure 1. mRNAs with alternative 5′‐UTRs can be generated either by the use of alternative promoters, which results in different transcription start sites (TSS1 and TSS2), or by alternative spicing events. In this way, alternative 5′‐UTRs corresponding to the same gene may contain different combinations of regulatory elements, as shown here. CDS, coding sequence; mG7, 7‐methyl‐guanylate; IRES, internal ribosome entry site; sAUG, start AUG; uAUG, upstream AUG and uORF, upstream open reading frame.

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